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A mechanism underlying dopamine D 1 and D 2 receptor‐mediated inhibition of dopaminergic neurones in the ventral tegmental area in vitro
Author(s) -
Momiyama Toshihiko,
Todo Naoyuki,
Sasa Masashi
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13710.x
Subject(s) - ventral tegmental area , dopaminergic , dopamine , neuroscience , dopamine receptor , mechanism (biology) , chemistry , dopaminergic pathways , in vitro , biology , biochemistry , physics , quantum mechanics
1 An intracellular recording study was performed to elucidate the mechanism underlying D 1 and D 2 receptor‐mediated inhibition of neuronal activities of dopaminergic neurones in the ventral tegmental area (VTA) using slice preparations of the rat brain. 2 VTA neurones were classified into type I and type II neurones according to the shape of the action potential, which correspond to dopaminergic and non‐dopaminergic neurones, respectively. 3 Addition of dopamine (10 μ m ) and quinpirole (1–100 μ m ) to the bath hyperpolarized the membrane of the type I neurones concomitantly with an increase in membrane conductance and an inhibition of action potentials which occurred spontaneously and were elicited by depolarizing pulses applied to the cell. However, quinpirole (10 μ m ) had no effect on the threshold for action potentials induced by a depolarizing pulse. 4 These quinpirole (10 μ m )‐induced effects were antagonized by simultaneous application of domperidone (5 μ m ), a D 2 receptor antagonist. 5 The amplitude of quinpirole (10 μ m )‐induced hyperpolarization was decreased by increasing the potassium concentration in the perfusing fluid or simultaneous application of tetraethylammonium (10 μ m ). 6 SKF 38393 (10 or 100 μ m ), a D 1 receptor agonist, had no effect on the resting membrane potential or action potential firing induced by a depolarizing pulse applied to the cell. However, when SKF 38393 (10 μ m ) was applied simultaneously with quinpirole (10 μ m ), the threshold for action potential generation was elevated by 5–6 mV, although there was no enhancement of hyperpolarization induced by quinpirole. 7 The elevation of the threshold for action potentials induced by SKF 38393 in the presence of quinpirole was antagonized by simultaneous application of SCH 23390 (5 μ m ), a D 1 receptor antagonist. 8 Dopamine (10 μ m ), quinpirole (10 or 100 μ m ) and SKF 38393 (10 or 100 μ m ) had no effect on the resting membrane potential or spontaneously occurring action potentials in type II neurones. 9 These findings suggest that activation of dopamine D 2 receptors of dopaminergic neurones in the VTA increases potassium conductance, thereby hyperpolarizing the membrane and eventually inhibiting neuronal activities. They also suggest that simultaneous activation of both D 1 and D 2 receptors enhances the D 2 receptor‐mediated inhibitory effects by elevation of the threshold for action potential generation.